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Accumulation of DC-SIGN+CD40+ dendritic cells with reduced CD80 and CD86 expression in lymphoid tissue during acute HIV-1 infection

Loré, Karina,b,*; Sönnerborg, Andersa,b; Broström, Christinab; Goh, Li-Eanc; Perrin, Lucd; McDade, Hughc; Stellbrink, Hans-Jürgene; Gazzard, Brianf; Weber, Rainerg; Napolitano, Laura A.h; van Kooyk, Yvettei; Andersson, Janb

Basic Science

Background: Dendritic cells (DC) are target cells for HIV-1 and play a key role in antigen presentation and activation of T cells.

Objective: To characterize interdigitating DC in lymphoid tissue (LT) with regard to maturation, expression of cytokines and co-stimulatory molecules in HIV-1-positive patients.

Methods: DC were characterized by immunohistochemistry and in situ imaging in LT from patients with acute HIV-1 infection (aHI), antiretroviral treated patients, long-term non-progressors/slow progressors with HIV-1 infection (LTNP/SLP), patients with AIDS, HIV-1-negative controls and patients with acute Epstein–Barr virus (EBV) infection.

Results: A significant increase of interdigitating DC expressing CD1a, S-100b, CD83 and DC-SIGN was found in LT from patients with aHI (P < 0.02). The co-stimulatory molecules CD80 and CD86 were, however, only partially upregulated and the complete parafollicular network found in acute EBV infection was not generated, despite increased expression of interleukins 1α, 1β, 12; interleukin 1α receptor antagonist; interferon α; and CD40 expression. LTNP/SLP and treated aviremic subjects had increased frequency of interdigitating DC, albeit lower than in aHI, and low expression of CD80 and CD86. In contrast, patients with AIDS had fewer DC and reduced cytokine expression in LT.

Conclusions: In the early phase of HIV-1 infection, there was a migration of DC to LT comparable to that found in acute EBV infection. The infiltration of DC in LT in acute EBV infection was accompanied by upregulation of CD80 and CD86 expression, which did not occur in aHI. This co-stimulatory defect in aHI may have an impact on the development of HIV-1-specific T cell immunity.

From the aDivision of Clinical Virology, Department of Microbiology, Pathology and Immunology and the bCenter for Infectious Medicine of the Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden, the cHIV Department, GlaxoWellcome R&D, Middlesex, UK, the dDepartment of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland, eMed. Poliklinik, Universitatsklinikum Eppendorf, Hamburg, Germany, fSt Stephen's Clinic, Chelsea & Westminster Hospital, London, UK, the gDepartment of Clinical Immunology, Royal Free Hospital, London, UK, the hGladstone Institute of Virology and Immunology, University of San Francisco, San Francisco, California, USA and the iDepartment of Molecular Cell Biology, Free University Medical Center Amsterdam, Amsterdam, the Netherlands. *Present address, National Institutes of Health, Vaccine Research Center, Bethesda, Maryland, USA.

Requests for reprints to: Dr K. Loré, National Institutes of Health, Vaccine Research Center, Bldg 40 Room 3612B, 40 Convent Drive, Bethesda, Maryland, USA. E-mail: klore@mail.nih.gov

Received: 18 July 2001;

revised: 19 October 2001; accepted: 1 November 2001.

Sponsorship: this work was supported by Glaxo Wellcome UK, the UCSF Center for AIDS Research (P30 MH59037), NIH grant CA66529 and A141536, the Swedish Physicians against AIDS research fund and the Swedish Medical Research Foundation grant 10850.

© 2002 Lippincott Williams & Wilkins, Inc.